Field of the Invention
The present invention relates to a time-of-flight mass spectrometer used in quantitative analysis and simultaneous qualitative analysis of trace compounds and also in structural analysis of sample ions. The invention also relates to a method of controlling this spectrometer.
Description of the Related Art
A mass spectrometer (MS) ionizes a sample in an ion source, separates the resulting ions in a mass analyzer at each value of m/z obtained by dividing the mass (m) by the charge number (z), and detects the separated ions by a detector. The results are represented in the form of a mass spectrum. On the horizontal axis of the spectrum, m/z values are plotted, while on the vertical axis, relative intensities are plotted. In this way, m/z values and relative intensities of compounds contained in the sample are obtained. Consequently, qualitative and quantitative information about the sample can be derived. Various methods are available as ionization method, mass separation method, and ion detection method for mass spectrometers.
A time-of-flight (TOF) mass spectrometer is an instrument that finds the mass-to-charge ratio (m/z) of each ion by accelerating ions with a given accelerating voltage, causing them to fly, and calculating the m/z from the time taken for each ion to reach a detector. In the TOF mass spectrometer, ions are accelerated by a constant pulsed voltage Va. At this time, from the law of conservation of energy, the following Eq. (1) holds.
                                          mv            2                    2                =                  zeV          a                                    (        1        )            where v is the velocity of the ion, m is the mass of the ion, z is the valence number of the ion, and e is the elementary charge.
From Eq. (1), the velocity v of the ion is given by
                    v        =                                            2              ⁢                                                          ⁢                              zeV                a                                      m                                              (        2        )            
Therefore, the flight time T required for the ion to reach a detector, placed behind at a given distance of L, is given by
                    T        =                              L            v                    =                      L            ⁢                                          m                                  2                  ⁢                                                                          ⁢                                      zeV                    a                                                                                                          (        3        )            
As can be seen from Eq. (3), the flight time T differs according to m/z of each ion. TOFMS is an instrument for separating ions employing this principle.
A linear TOF mass spectrometer in which ions are made to fly linearly from an ion source to a detector and a reflectron TOF mass spectrometer in which a reflectron field is placed between an ion source and a detector to improve energy focusing and to prolong the flight distance have enjoyed wide acceptance. It is known that reflectron TOF mass spectrometers are used to estimate the compositions of unknown substances, because they can measure the m/z values of unknown substances with errors on the order of ppm with respect to m/z values computationally found from composition formulas.
The mass resolution R of a TOF mass spectrometer is defined as follows:
                    R        =                  T                      2            ⁢                                                  ⁢            Δ            ⁢                                                  ⁢            T                                              (        4        )            where T is the total flight time and ΔT is a peak width.
That is, if the peak width ΔT is made constant and the total flight time T can be lengthened, the mass resolution can be improved. However, in the related art linear or reflectron type TOFMS, increasing the total flight time T (i.e., increasing the total flight distance) will lead directly to an increase in instrumental size. A multi-pass time-of-flight mass spectrometer has been developed to realize high mass resolution while avoiding an increase in instrumental size (non-patent document 1). This instrument uses four toroidal electric fields each consisting of a combination of a cylindrical electric field and a Matsuda plate. The total flight time T can be lengthened by accomplishing multiple turns in an 8-shaped circulating orbit. In this apparatus, the spatial and temporal spread at the detection surface has been successfully converged up to the first-order term using the initial position, initial angle, and initial kinetic energy.
However, the TOFMS in which ions revolve many times in a closed trajectory suffers from the problem of “overtaking”. That is, because ions revolve multiple times in a closed trajectory, lighter ions moving at higher speeds overtake heavier ions moving at smaller speeds. Consequently, the fundamental concept of TOFMS that ions arrive at the detection surface in turn first from the lightest one does not hold.
The spiral-trajectory TOFMS has been devised to solve this problem. The spiral-trajectory TOFMS is characterized in that the starting and ending points of a closed trajectory are shifted from the closed trajectory plane in the vertical direction. To achieve this, in one method, ions are made to impinge obliquely from the beginning (patent document 1). In another method, the starting and ending points of the closed trajectory are shifted in the vertical direction using a deflector (patent document 2). In a further method, laminated toroidal electric fields are used (patent document 3).
Another TOFMS has been devised which is based on a similar concept but in which the trajectory of the multi-pass TOF-MS (patent document 4) where overtaking occurs is zigzagged (patent document 5).
As described previously, in a mass spectrometer, ions generated in an ion source are separated according to m/z value in a mass analyzer and detected. The results are expressed in the form of a mass spectrum in which the m/z values of ions and their relative intensities are graphed. This measurement may hereinafter be referred to as an MS measurement in contrast with an MS/MS measurement. In the MS/MS measurement, certain ions generated in an ion source are selected by a first stage of mass analyzer (hereinafter referred to as MS1). The selected ions are referred to precursor ions. These ions spontaneously fragment or are caused to fragment, and the generated, fragmented ions (referred to as product ions) are mass analyzed by a subsequent stage of mass analyzer (referred to as MS2). An instrument enabling this is referred to as an MS/MS instrument. In MS/MS measurements, the m/z values of precursor ions, the m/z values of product ions generated in plural fragmentation paths, and information about relative intensities are obtained and so structural information about the precursor ions can be obtained. Various types of MS/MS instrument exist which can perform MS/MS measurements and in which two of the aforementioned mass spectrometers are combined. Furthermore, various fragmentation methods exist such as collision induced dissociation (CID) using collision with gas, photodissociation, and electron capture dissociation.
Dissociation information about an MS/MS instrument utilizing CID differs according to collisional energy, i.e., the magnitude of kinetic energy of ions impinging on a collisional cell. In the case of currently available MS/MS instruments, CIDs are classified into two types: CIDs of low energies on the order of tens of eV and CIDs of high energies from several kV to tens of keV. The difference depends on the configuration of the instrument. High-energy CID has the advantage that, when a peptide having tens of amino acids chained together is fragmented, side chain information may be obtained. It is possible to distinguish between leucine and isoleucine having the same molecular weight.